Neulasta (peg-filgrastim; G-CSF) Neupogen (filgrastim; G-CSF) Neulasta Onpro (peg-filgrastim; G-CSF) Leukine (sargramostim; GM-CSF) General Authorization Criteria for ALL Agents and Indications: Prescribed by, or in consultation with, a hematologist or oncologist Medical records, including labs and weight or body surface area (BSA), to support diagnosis and dosing is submitted with request Requested agentis dosed and administered within Food and Drug Administration (FDA)labeledrecommendations o Will not be used concomitantly with radiation AND chemotherapy o Will be administeredatthe appropriate time after chemotherapy OR radiation Member does not have any contraindications or hypersensitivity to the requested agent Will not be used in combination with other myeloid growth factors Additional Criteria Based on Indication: Chemotherapy-Induced Febrile Neutropenia: (Neupogen, Neulasta, and Leukine) Member is receiving chemotherapy for a NON-myeloid cancer (i.e., solid tumor, lymphoma) o For PRIMARY prophylaxis: Member meets one of the following: Chemotherapy regimen isgiven after bone marrow transplant; OR Chemotherapy regimen has >20% risk of febrile neutropenia;or Chemotherapy regimen has 10%-20% risk of febrile neutropenia AND member has ANY of the following risk factors for febrile neutropenia: o age > 65 years o prior chemotherapy or radiation therapy o persistent neutropenia o bone marrow involvement by tumor o Recent surgery and or open wounds o Liver dysfunction (bilirubin > 2.0) o Renal dysfunction (creatinine clearance (CRCL) <50) o For SECONDARY pr ophylaxis (Neupogen, Neulasta, andleukine): Member previously experienced febrile neutropenia from the same chemotherapy regimen and reducing or delaying chemotherapy dose may compromise treatment outcome o For TREATMENT of febrile neutropenia (Leukine and Neupogen) in members who did NOT receive colony stimulating factor (CSFs) prophylaxis: Member has risk factors for poor outcomes resulting from febrile neutropenia (e.g., age > 65, sepsis, severe neutropenia (absolute neutrophil count (ANC)< 100/mcL), current infection, hospitalized at onset of fever, prior episode of febrile neutropenia) Severe chronic congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia: (Neupogen) o Member has one of the following: Effective: 2/1/2018 Page 1
Evidence of inadequate bone marrow reserve (e.g., recurrentfevers, splenomegaly, mucosal ulcers, abdominal pain) Highrisk for developing serious bacterialinfection (e.g., primarily severe neutropenia, indwelling venous catheters, prior serious infections) Current bacterial infection Neutropeniarelated tohuman Immunodeficiency Virus (HIV) or drug therapy; ganciclovir or zidovudine induced: (Neupogen and Leukine) o Prescribed by, or in consultation with an Infectious Disease Specialist, Hematologist, or Human Immunodeficiency Virus (HIV)Specialist Neupogen may also be approved if medically necessary for the following indications: o Acute MyeloidLeukemia in members receiving induction or consolidation chemotherapy o Mobilizationof hematopoietic progenitor cells before autologous stem celltransplant o Mobilization of hematopoietic progenitor cells in the donor before allogenic stem cell transplant o Treatment of acute radiation exposure in members who receive myelosuppressive doses of radiation at a dose of 2 gray (Gy) o Myelodysplastic Syndrome (MDS) or aplastic anemia in a member with anabsolute neutrophil count (ANC) <500 Leukine may also be approved if medically necessary for the following indications: o Acute Myeloid Leukemia after induction chemotherapy for members age 55 years or older o Bone marrow transplantfailure orengraftment delay o Myeloid reconstitution after allogenic bone marrow transplant o Myeloid reconstitution after autologous bone marrow transplant inmembers with Hodgkin s disease, non Hodgkin's lymphoma, or acute lymphocytic leukemia o Before and after autologous peripheral blood stem cell transplantation Initial Approval: Chemotherapy-induced neutropenia (primary or secondary prophylaxis): o Approve per cycle of chemotherapy: Up to a 14 day supply for Neupogen, and Leukine One (1) 6 mg dose of Neulasta no less than every 14 days Include refills if number of cycles is provided o Treatment of neutropenia (e.g., congenital, cyclic, or idiopathic, Human Immunodeficiency Virus(HIV), or after chemo + bone marrow transplant (BMT)): Approve for 3 months For other indications o Up to six months or less Renewal: Chemotherapy-induced neutropenia (primary or secondary prophylaxis): o Recent absolute neutrophil count (ANC) showing a response totherapy o Approve per cycle of chemotherapy: Up to a 14 day supply for Neupogen, and Leukine Effective: 2/1/2018 Page 2
One (1) 6 mg dose of Neulasta no less than every 14 days Include refills if number of cycles is provided, or up to 12 months All other indications: o Recent absolute neutrophil count (ANC), complete blood count (CBC), and/or platelet counts o Approve up to one year Additional Information: Note: Neutropenia is defined as an absolute neutrophil count (ANC) of < 500 neutrophils/mcl or an absolute neutrophil count (ANC) of < 1000 neutrophils/mcl and a predicted decline to < than or equal to500 neutrophils/mcl over the next 48 hours. Determining the risk of febrile neutropenia: A member s risk for developing neutropenic fever may be assessed prior to the use of colony stimulating factors. This may be achieved by evaluating the degree of myelosuppression of the member s chemotherapy regimen in addition to the presence of other member-related risk factors. Both Infectious Diseases Society of America (IDSA) and National Comprehensive Network (NCCN)recommend that colony stimulating factors be considered when the risk of febrile neutropenia is>20%. Dosing Table: Medication Dosing Available Dosage forms Neupogen Febrile Neutropenia (FN) or acute myeloid leukemia (AML): 5 Vials: mcg/kg/day (Not given 24 hours before chemotherapy 300 mcg/ml, single-dose vial and 24 hours after) 480 mcg/1.6 ml, single-dose vial Bone marrow transplant (BMT): 10 mcg/kg/day (given 24 hrs after bone marrow transplant (BMT) and given for at least 24 hours) Prefilled Syringe 300 mcg/0.5 ml per syringe 480 mcg/0.8 ml per syringe Neulasta Leukine Peripheral Blood Progenitor Cell (PBPC): 10 mcg/kg/day; at least 4 days before and up to 7 days Severe Chronic Neutropenia: o Idiopathic neutropenia:1.2 mcg/kg/day o Cyclic neutropenia: 2.1 mcg/kg/day o Congenital neutropenia: 6 mcg/kg/day divided 2 times per day Febrile Neutropenia- 5mcg/kg/day Not given 24 hours before chemotherapy and 24 hours after chemotherapy Given once per chemotherapy cycle Acute myeloid leukemia (AML): 250 mcg/m 2 /day subcutaneous (SQ) or intravenous (IV) on day 11 or 4 days following the completion of induction chemotherapy 6 mg/0.6 ml, single-dose prefilled syringe 6 mg/0.6 ml, single-dose prefilled syringe co-packaged with the Onbody Injector (Neulasta Onpro kit). 500 mcg/ml vial 250 mcg powder for injection Effective: 2/1/2018 Page 3
References: 1. National Comprehensive Network (NCCN) Clinical Practice Guidelines in Oncology: Myeloid Growth 2. Factors V.1.2015. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloid_growth.pdf. Accessed August 16, 2017 3. Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline. J Clin Oncol 24:3187-3205. Available at: http://jco.ascopubs.org/cgi/reprint/24/19/3187. Accessed August 16, 2017 4. National Comprehensive Network (NCCN) Clinical Practice Guidelines in Oncology: Prevention and Treatment of - Related Infection. V.2.2015. Available at: http://www.nccn.org/professionals/physic ian_gls/pdf/infections.pdf Accessed Oct 5, 2015. 5. Infectious Disease Society of America: Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Members with : 2010 Update by the Infectious Diseases Society of America. Available at: http://news.idsociety.org/idsa/issues/2011-01-01/17.html Accessed August 16, 2017 6. Zarxio (filgrastim-sndz) [package insert]. Princeton, NJ: Sandoz Inc. December 2014 7. Granix(tbo-filgrastim) [package insert]. North Wales, PA: Cephalon,Inc.July 2015 8. Neupogen [package insert]. Thousand Oaks,CA: Amgen,Inc June 2016 9. Levine JD, Allan JD, Tessitore JH, Falcone N, Galasso F, Israel RJ, Groopman JE. Recombinant human granulocyte-macrophage colony-stimulating factor ameliorates zidovudine-induced neutropenia in members with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex. Blood. 1991;78:3148 3154. 10. Hermans P, Rozenbaum W, Jou A, et al. Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group. AIDS. 1996;10(14):1627-1633. 11. Hermans P, Rozenbaum W, Jou A, et al. Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group. AIDS. 1996;10(14):1627-1633. Table: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 20% or Higher Histology Treatment Setting Regimen Acute Lymphoblastic Leukemia (ALL) Induction ALL induction regimens (see NCCN guidelines) Bladder Neoadjuvant, adjuvant, metastatic Prior adjuvant allowed MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) CBDCa/Pac (carboplatin, paclitaxel) Breast Metastatic or relapsed Docetaxel + trastuzumab Effective: 2/1/2018 Page 4
Esophageal and Gastric s Hodgkin Lymphoma Kidney Non-Hodgkin's Lymphoma Metastatic (1st line) Metastatic (2nd line) Diffuse large B-cell lymphoma {DLBCL], peripheral T-cell lymphomas (PTCL], 2nd line DLBCL, 2nd line, refractory PTCL, DLBCL, 2nd line DLBCL, PTCL, 2nd line, recurrent Relapsed Dose-dense AC followed by T (doxorubicin, cyclophosphamide, paclitaxel) TAC (docetaxel, doxorubicin, cyclophosphamide) AT (doxorubicin, docetaxel) Doc (docetaxel) Docetaxel/cisplatin/fluorouracil BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) Doxorubicin/gemcitabine ICE (ifosfamide, carboplatin, etoposide) RICE (rituximab, ifosfamide, carboplatin, etoposide) CHOP-14 (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab MINE (mesna, ifosfamide, novantrone, etoposide) DHAP (dexamethasone, cisplatin, cytarabine) ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine (Ara-C)) HyperCVAD + rituximab (cyclophosphamide, vincristine, doxorubicin, dexamethasone + rituximab) VAPEC-B (vincristine, doxorubicin, Effective: 2/1/2018 Page 5
Melanoma Ovarian Pancreatic Soft Tissue Sarcoma Small Cell Lung Pharmacy Prior Authorization Advanced, metastatic, or recurrent Advanced, metastatic, or recurrent Advanced or metastatic Recurrent prednisolone, etoposide, cyclophosphamide, bleomycin) Dacarbazine-based combination (dacarbazine, cisplatin, vinblastine) Dacarbazine-based combination with IL-2, interferon alpha (dacarbazine, cisplatin, vinblastine, IL-2, interferon alpha) Topotecan Paclitaxel Docetaxel FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) MAID (mesna, doxorubicin, ifosfammide, dacarbazine) Doxorubicin Ifosfamide/doxorubicin Top (topotecan) CAV (cyclophosphamide, doxorubicin, vincristine) Testicular cancer Relapsed VelP (vinblastine, ifosfamide, cisplatin) Source: Smith, et al., 2006; NCCN, 2016. VIP (etoposide, ifosfamide, cisplatin) BEP (bleomycin, etoposide, cisplatin) TIP (paclitaxel, ifosfamide, cisplatin) Table: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 10% to 19% Histolog y Treatment Setting Regimen Effective: 2/1/2018 Page 6
Occult primary - adenocarcinom a Gemcitabine/docetaxel Breast cancer Cervical (taxane portion only) Metastatic (1st line) Metastatic (1st line) Metastatic (2nd line) Metastatic or relapsed Docetaxel every 21 days CMF classic (cyclophosphamide, methotrexate, fluorouracil) CA (doxorubicin, cyclophosphamide) (60 mg/m2) (hospitalized) AC (doxorubicin, cyclophosphamide) + sequential docetaxel AC + sequential docetaxel + trastuzumab A (doxorubicin) (75) AC (doxorubicin, cyclophosphamide) CapDoc (capecitabine, docetaxel) FEC (fluorouracil, epirubicin, cyclophosphamide) + sequential docetaxel Paclitaxel every 21 days TC (docetaxel, cyclophosphamide) FOLFOX (fluorouracil, leucovorin, oxaliplatin) Colorectal Advanced FL (fluorouracil, leucovorin) Esophageal and Gastric s Advanced (one prior chemo allowed) CPT-11 (irinotecan) (350 mg/m2 q 3 wk) Irinotecan/cisplatin Epirubicin/cisplatin/5-fluorouracil Epirubicin/cisplatin/capecitabine Head and Neck Induction Cis/Doc/5-FU (cisplatin, docetaxel, 5-fluorouracil) Effective: 2/1/2018 Page 7
Multiple myeloma Non-Hodgkin's lymphomas Non-Small Cell Lung Pharmacy Prior Authorization AIDS-related NHL, Burkitt lymphoma, recurrent, otehr NHL subtypes AIDS-related NHL, DLBCL, recurrent DLBCL, PTCL, 2nd line DLBCL, 2nd line, Burkitt lymphoma, other NHL subtypes Advanced/metasta tic, advanced/metastat ic, advanced/metastat ic, advanced/metastat ic, advanced/metastat DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophoaphamide/eto poside) DT-PACE + bortezomib (VTD-PACE) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) EPOCH-IT chemotherapy GDP (gemcitabine, dexamethasone, cisplatin) GDP (gemcitabine, dexamethasone, cisplatin) + rituximab FMR (fludarabine, mitoxantrone, rituximab) CHOP + rituximab (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) including regimens with pegylated liposomal doxorubicin or mitoxantrone substituted for doxorubicin Cisplatin/paclitaxel Cisplatin/vinorelbine Cisplatin/docetaxel Cisplatin/etoposide Carboplatin/paclitaxel Effective: 2/1/2018 Page 8
ic Advanced/metasta tic Docetaxel Ovarian Pancreatic Prostate Small Cell Lung Testicular Uterine Sarcoma Advanced or metastatic Carboplatin/docetaxel FOLFIRINOX Cabazitaxel Etoposide/carboplatin Etoposide/carboplatin Docetaxel Effective: 2/1/2018 Page 9